Drugs of abuse elicit dopamine release unconditionally, sensitizing the reward system to drugs and drug-associated stimuli resulting in compulsive drug-seeking and drug-taking behaviour. It has been discovered that these same dopamine neurons consistently respond to natural rewards when the reward delivery is at maximum uncertainty (50%). Reward uncertainty is a defining feature of gambling. Therefore, chronic increases in dopamine release from gambling-like stimuli could lead to sensitization of the reward pathways and contribute to gambling pathology. This study investigated the effects of repeated exposure to different probabilities of sucrose reward (0, 25%, 50%, 75%, 100%) on sensitivity to an amphetamine challenge (0.5 mg/kg) and development of sensitization after multiple amphetamine doses (5 x 1.0/kg) in Sprague–Dawley and Lewis rats. No significant group differences were found during the amphetamine challenge or amphetamine sensitization in either strain. Opportunities for improvement in the experimental paradigm and for future research are discussed.

Drugs of abuse elicit dopamine release unconditionally, sensitizing the reward system to drugs and drug-associated stimuli resulting in compulsive drug-seeking and drug-taking behaviour. It has been discovered that these same dopamine neurons consistently respond to natural rewards when the reward delivery is at maximum uncertainty (50%). Reward uncertainty is a defining feature of gambling. Therefore, chronic increases in dopamine release from gambling-like stimuli could lead to sensitization of the reward pathways and contribute to gambling pathology. This study investigated the effects of repeated exposure to different probabilities of sucrose reward (0, 25%, 50%, 75%, 100%) on sensitivity to an amphetamine challenge (0.5 mg/kg) and development of sensitization after multiple amphetamine doses (5 x 1.0/kg) in Sprague–Dawley and Lewis rats. No significant group differences were found during the amphetamine challenge or amphetamine sensitization in either strain. Opportunities for improvement in the experimental paradigm and for future research are discussed.